Minimal RNA aptamer sequences that can inhibit or alleviate noncompetitive inhibition of the muscle-type nicotinic acetylcholine receptor.
Submitted by Oné R Pagán on
Title | Minimal RNA aptamer sequences that can inhibit or alleviate noncompetitive inhibition of the muscle-type nicotinic acetylcholine receptor. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Sivaprakasam, K, Pagán, OR, Hess, GP |
Journal | J Membr Biol |
Volume | 233 |
Issue | 1-3 |
Pagination | 1-12 |
Date Published | 2010 Feb |
ISSN | 1432-1424 |
Keywords | Animals, Aptamers, Nucleotide, Base Sequence, Cell Line, Cocaine, Dizocilpine Maleate, Kinetics, Mice, Models, Theoretical, Molecular Sequence Data, Nucleic Acid Conformation, Receptors, Nicotinic |
Abstract | Combinatorially synthesized nucleotide polymers have been used during the last decade to find ligands that bind to specific sites on biological molecules, including membrane-bound proteins such as the nicotinic acetylcholine receptors (nAChRs). The neurotransmitter receptors belong to a group of four structurally related proteins that regulate signal transmission between ~10(11) neurons of the mammalian nervous system. The nAChRs are inhibited by compounds such as the anticonvulsant MK-801 [(+)-dizocilpine] and abused drugs such as cocaine. Based on predictions arising from the mechanism of receptor inhibition by MK-801 and cocaine, we developed two classes of RNA aptamers: class I members, which inhibit the nAChR, and class II members, which alleviate inhibition of the receptor by MK-801 and cocaine. The systematic evolution of ligands by the exponential enrichment (SELEX) method was used to obtain these compounds. Here, we report that we have truncated RNA aptamers in each class to determine the minimal nucleic acid sequence that retains the characteristic function for which the aptamer was originally selected. We demonstrate that a truncated class I aptamer containing a sequence of seven nucleotides inhibits the nAChR and that a truncated class II aptamer containing a sequence of only four nucleotides can alleviate MK-801 inhibition. |
DOI | 10.1007/s00232-009-9215-z |
Alternate Journal | J. Membr. Biol. |
PubMed ID | 20049590 |
Grant List | DA 11643 / DA / NIDA NIH HHS / United States F34 GM20771 / GM / NIGMS NIH HHS / United States |